Specific Aims: 1. To evaluate anti-HIV-1 human Fab fragments generated in the first phase of this project and in Aim 2 in terms of breadth and potency of neutralization of primary isolates, epitope recognized, neutralization synergy, mechanisms of neutralization escape and potential mimetopes. 2. To generate new human anti-HIV-1 antibodies (i) for Aim 1 and (ii) to provide insight into the interplay of virus and antibody. Particular attention will be paid to long-term non-progression with broad neutralizing serum antibody activity to primary isolates as library donors. To evaluate in vitro evolved and whole antibody versions of the Fabs from Aims 1 and 2 in parameters of primary isolate neutralization for inclusion in a cocktail of antibodies for passive immunization. It is envisaged the cocktail will comprise 3-6 antibodies against distinct epitopes on the envelope of HIV-1. 4. To explore the features of antibody recognition of viral envelope which lead to potent neutralization of primary isolates. The plan is to 1. extend passive immunization studies to the SHIV/macaque model. 2. to pursue selection strategies and serology studies to explain the broad primary isolate neutralizing titers of two donors. 3. to define the epitopes recognized by neutralzing antibodies produced by infection with glycosyl-deficient SIV. 4. to explore the reasons for the broad neutralization resistance of some primary viruses. GCRC Normal Blood Donors (SPID 0075) are essential to this project.